Mussel adhesive proteins (MAPs) are remarkable underwater adhesive polymers that form tenacious bonds to anchor marine organisms onto the substrates upon which they reside. Even in the presence of water, the adhesive protein plaques form extremely tenacious bonds to solid objects, an accomplishment which is not often matched by synthetic adhesives. Because of these properties as well as many similarities between the marine and physiologic environment, there is great interest in mimicking MAPs in synthetic polymers for use as adhesives in dentistry and medicine. However, these efforts are hampered by a lack of detailed understanding of the molecular mechanism of MAP adhesion. The goals of this research are to employ nano-, micro- and macro-scale adhesion experiments to gain a detailed understanding of the adhesive role of L-3,4-dihydroxyphenylalanine (DOPA) and other key residues in mussel adhesion, and to use this information to motivate the design of new MAP-inspired macromolecular biomaterials. Single molecule force probe measurements will be performed to investigate the bond forces and energies associated with interaction of DOPA and DOPA-containing peptides with representative implant materials as well as hard and soft tissues. To complement the single molecule experiments, the adhesive strength arising from contact of ensembles of peptides presented at the surfaces of hydrogels with implant materials and tissues will be tested using a fracture micromechanics methodology. Finally, the information obtained from the nano- and micro-scale adhesion experiments will be exploited for rational design of new MAP mimetic polymers. These polymers will be synthesized and tested as hard and soft tissue adhesives using macro-scale lap shear bond strength measurements. This study will provide new insights into the fundamental role of DOPA and other amino acids in biological adhesion, and will generate new adhesive biomaterials for use in soft and hard tissue repair, tissue regeneration, and drug delivery. [unreadable] [unreadable] [unreadable]